[National evaluation of the diagnosis of activated protein C resistance]. / Evaluación nacional del diagnóstico de la resistencia a la proteína C activada.

Thrombophilia or prothrombotic state appears when activation of blood hemostatic mechanisms overcomes the physiological anticoagulant capacity allowing a thrombotic event. Thrombosis is the leading worldwide mortality cause and due to its high associated morbidity and mortality, it should be insisted in the opportune identification of a thrombophilic state. The study of thrombophilia identifies individuals at high risk for thrombosis. This meeting was conceived first to analyze the current status of the diagnosis of thrombophilia in Mexico and second to create the base for a national consensus for thrombophilia screening and for the establishment of a national center for laboratory reference and quality control for thrombophilia. Since searching of activated protein C resistance (APCR) and FV Leiden seem to have priority either in the clinical setting and in public health services, it was decided to start with these two abnormalities as a model to analyze the current status of thrombophilia diagnosis in the clinical laboratory. At this time, several thrombophilic abnormalities have been described however, APCR remains the most important cause of thrombophilia, accounting for as much as 20% to 60% of all venous thrombosis. APCR is a consequence of the resistance of activated FV to be inactivated by activated protein C. Procoagulant activity of activated FV increases the risk of thrombosis. Hereditary APCR is almost always due to a point mutation at the nucleotide 1691 of the FV gen inducing an Arg506Glu substitution in FV molecule. This mutation is better known as FV Leiden. Heterocygous carriers of FV Leiden have a thrombotic risk 5 to 10 times higher than general population while the risk for the homocygote state is increased 50 to 100-fold. When activated PC is added to plasma from patients with FV Leiden, this last resists the anticoagulant effect of activated PC. Therefore, thrombin production is not inhibited. This phenomenon is called APCR. The functional test evaluates the partially activated thromboplastin time (aPTT) in a plasma sample before and after adding activated PC. The result is reported as a standardized sensibility index: aPTT post-activated PC/aPTT pre-activated PC. The conclusions of this national reunion pretend to optimize the available resources in our country in order to allow a wide and less-expensive diagnosis of patients with thrombosis.

Primary thrombophilia in Mexico III: A prospective study of the sticky platelet syndrome.

During an 18-month period, 10 consecutive Mexican mestizos with a dinical marker associated with a primary hypercoagulable state were studied. The assessment of the sticky platelet syndrome (SPS) was done by the method described by Mammen. In addition, the activated protein C resistance phenotype, coagulation protein C activity and antigen, coagulation protein S, antithrombin III, plasminogen, tissue-type plasminogen activator activity, plasminogen activator inhibitor activity, plasminogen activator inhibitor type 1, IgG and IgM isotypes of anti-phospholipid antibodies, homocysteine levels, the factor V gene Leiden mutation, the 677 C->T mutation in the 5,10-methylen-tetrahydrofolate-reductase (MTHFR), and the G20210A polymorphism in the 3'-untranslated region of the prothrombin gene were studied. Six patients with the SPS were identified: only one displayed this as the single thrombophilic abnormality; in five others, additional thrombosis-prone conditions were found: heterozygosity for the MTHFR 677 gene mutation in five cases; and, in one case each, heterozygosity for the factor V Leiden mutation, heterozygosity for the factor II G20210A mutation, and antiphospholipid antibodies in another. Four of the six patients had a family history of thrombophilia. All patients were treated with aspirin and no new vasoocclusive episodes have been recorded. SPS in not an infrequent finding in Mexican mestizo thrombophilic patients and may contribute to thrombophilia.